CAMBRIDGE, Mass.—Infinity Pharmaceuticals Inc. and Bristol-Myers Squibb are doubling down with the announcement of an expansion of their ongoing clinical collaboration, which is focused on investigating IPI-549 in combination with Opdivo. With this expansion, the Phase 1/1b study will now include patients with triple-negative breast cancer who have not previously been treated with either anti-PD-1 or anti-PD-L1 therapy. IPI-549—an oral, selective phosphoinositide-3-kinase gamma (PI3K-gamma) inhibitor that targets immune-suppressive tumor macrophages—is being assessed in a Phase 1/1b in patients with advanced solid tumors.

The goals of the study are to determine the safety, tolerability, activity, pharmacokinetics and pharmacodynamics of IPI-549, both as a monotherapy and in combination with Opdivo. The study consists of monotherapy and combination dose-escalation components, as well as monotherapy expansion and combination expansion components. Enrollment for the monotherapy dose-escalation is complete, while monotherapy expansion is ongoing. The combination dose-escalation is ongoing, and it's expected that combination expansion will begin in the second half of the year. That latter component features several cohorts that will evaluate IPI-459 in patients with a variety of cancer types, including non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, and, thanks to the collaboration expansion, triple-negative breast cancer.

"The expansion of our ongoing clinical study of IPI-549 and our clinical collaboration with Bristol-Myers Squibb represents an important component of our strategy to bring better treatment options to patients," Adelene Perkins, CEO of Infinity, said in a press release. "Particularly, expanding our study to include patients with triple-negative breast cancer who have not been previously treated with a PD-1 or PD-L1 immune checkpoint inhibitor allows us to evaluate whether IPI-549 in combination with Opdivo can increase the number of patients who respond to checkpoint inhibition. To date, very few patients with triple-negative breast cancer respond to checkpoint inhibitors alone, leaving these patients with very limited therapeutic options."

IPI-549 selectively inhibits PI3K-gamma. In preclinical studies, the compound was seen to reprogram macrophages from a pro-tumor (M2) to an anti-tumor (M1) phenotype and proved capable of overcoming resistance to checkpoint inhibition and boosting the activity of checkpoint inhibitors. It's thought that IPI-549 could treat a variety of solid tumors in addition to restoring anti-tumor immunity when administered in combination with other immunotherapies. Given IPI-549's ability to reprogram macrophages, part of the Phase 1/1b study is designed to look at the potential of combining it with checkpoint inhibitors to see if the combination can overcome resistance in patients previously treated with checkpoint inhibition.

This is not the only partnering news for Bristol-Myers Squibb this week. In another cancer-focused arrangement, the company shared news of a clinical trial collaboration with AbbVie to test another immuno-oncology combination: ABBV-399, AbbVie's investigational antibody-drug conjugate, and Opdivo. The companies will be pitting this combination against c-Met overexpressing non-small cell lung cancer (NSCLC). A Phase 1b clinical study, sponsored by AbbVie, is aimed at determining the tolerability and efficacy of this combination approach in NSCLC patients who have failed one prior line of chemotherapy. As with the Bristol-Myers Squibb/Infinity agreement, this trial could be expanded to include other solid tumors down the line.

“We continue to explore the potential of novel combinations of medicines with Opdivo, and AbbVie’s investigational treatments will help evaluate the role of new targets in combination with immunotherapy” said Dr. Fouad Namouni, head of Development, Oncology, at Bristol-Myers Squibb. “We look forward to continuing to partner our PD1 with AbbVie’s early- and late-stage assets as a possible treatment option for patients with lung cancer.”